Abstract
Objective: 1) Report isolation of HPV-11 with viral genome duplication in the lung tumor lesions of a 23-year-old man with a 20-year history of recurrent respiratory papillomatosis (RRP). 2) Describe pulmonary RRP response to vorinostat therapy, following previous disease progression on alpha-interferon, intralesional cidofivir, and oral methotrexate.
Method: Following RUL segmentectomy to remove a 4-cm RRP lesion and laser ablation of laryngeal papillomas, HPV viral genome was isolated and sequenced. Lung tumor cells were screened for in vitro sensitivity to multiple therapies, including vorinostat. Success of vorinostat therapy was measured by radiologic evaluation of lung lesions.
Results: HPV-11 DNA was isolated from laryngeal and pulmonary lesions. Genomic sequencing identified a 2kB duplication of the HPV-11 genome in the lung lesions only, including a novel duplication of the upstream promoter and the E6/E7 oncogenes. Lung tumor cells demonstrated in vitro sensitivity to vorinostat. After 12 weeks of vorinostat therapy (tolerated at 400 mg/daily for 21 days q 4 weeks), repeat CT revealed significant reduction of most lung lesions compared to baseline. Pulmonary and laryngeal diseases remained stable after 12 months follow-up on vorinostat.
Conclusion: We present the first documented case of progressive, chemoresistant pulmonary RRP responsive to vorinostat. Our data suggest a link between the duplication of HPV-11 promoter and viral oncogenes and aggressive clinical phenotype. Use of novel cell-culture technology and in vitro chemosensitivity screening may improve long-term prognosis of this notoriously recalcitrant disease.
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